It is proposed to study the underlying mechanisms of toxicity of bacterial endotoxins by examining interrelationships between the toxin, the prostaglandins and the catecholamines. The involvement of certain other vasoactive agents known to be released by the triggering action of endotoxin will be investigated also: these include serotonin, histamine and bradykinin. Selective inhibitors will be used to aid in the elucidation of specific roles of the vasoactive agents exhibiting activity in the experimental models to be employed. The principal animal models will be the normal and pregnant mouse and the in situ and autotransplanted spleen and uterus of the sheep. In the latter models, additional experiments will be conducted on the importance of sympathetic innervation for the release of vasoactive agents and on changes in vascular permeability under the influence of endotoxin, prostaglandins and other vasoactive agents.